crossing96/oncoscreening huggingface dataset:
Lymph node metastasis mapping in extended lymphadenectomy to the level of the inferior mesenteric artery for bladder cancer.	BACKGROUND: The aim of this study was to evaluate the distribution of lymph node metastasis in extended lymphadenectomy for patients with bladder cancer. METHODS: We analyzed 31 patients who underwent extended lymphadenectomy at radical cystectomy for bladder cancer between April 2008 and February 2010. Specimens were evaluated as 14 separate packages from predesignated anatomical locations. The lymph node mapping was prospectively registered. RESULTS: The median lymph node count was 37 (range 19-68). Ten (32%) patients had lymph node metastasis. The positive rates at each lymph node site were 0% at the left internal iliac, 13% at the left obturator, 3.2% at the left external iliac, 6.5% at the right internal iliac, 10% at the right obturator, 16% at the right external iliac, 3.2% at the left common iliac, 3.2% at the right common iliac and 6.5% at the presacral node. No lymph node metastasis was detected in the Cloquet, paracaval, aortocaval or paraaortic nodes. One (3.2%) patient had a skip metastasis from the left obturator to the presacral node. CONCLUSIONS: Extended lymphadenectomy provides more accurate lymph node staging. We suggest that it is better to perform lymphadenectomy at least below the aortic bifurcation including the presacral node.	bladder
Analysis of prognostic factors of pediatric-type sarcomas in adult patients.	OBJECTIVE: Pediatric-type sarcomas such as Ewing's sarcoma (EWS)/primitive neuroectodermal tumor family and rhabdomyosarcoma are relatively uncommon in adult patients. Optimal treatment strategies for this population and prognosis in adult patients compared with pediatric patients remain controversial. METHODS: We retrospectively reviewed pediatric-type sarcoma patients older than 15 years at a single institution. RESULTS: A total of 84 consecutive patients between 1995 and 2009 were identified at the Samsung Medical Center, Seoul, Korea. Median age was 30 years with a range of 15-74 years. Forty-seven patients (56.0%) were diagnosed with Ewing's sarcoma/primitive neuroectodermal tumor family, 34 (40.5%) with rhabdomyosarcoma and 3 (3.6%) with desmoplastic round-cell tumor. Median follow-up duration was 5.9 years. Median overall survival for all patients was 33.1 months (95% CI 13.5-52.7) and median event-free survival for all patients was 14.4 months (95% CI 5.9-22.9 months). Multivariate analysis revealed that localized disease was a significant independent prognostic factor for longer overall survival (hazard ratio 0.30, 95% CI 0.14-0.66, p = 0.003), and favorable primary tumor sites were associated with longer event-free survival (hazard ratio 0.33, 95% CI 0.11-0.98, p = 0.045). CONCLUSION: We identified the prognostic variables which may facilitate risk-adapted therapies for this rare adult sarcoma group, which should be further investigated.	bladder
Analysis of promoters and expression-targeted gene therapy optimization based on doubling time and transfectability.	Genes under the control of the cyclooxygenase-2 (Cox-2), human epidermal growth factor receptor 2 (Her-2), and survivin promoters were constructed and delivered to murine and human carcinoma cells. It was found that (P)Cox-2-driven reporter expression was strong and correlated well with endogenous Cox-2 levels, while (P)Her-2 and (P)survivin yielded poor results, consistent with the three distinct expression mechanisms used by cancer cells to overexpress the endogenous versions of the selected genes. The (P)Cox-2 was then used to drive the expression of caspase genes both in vitro and in vivo to bring about targeted apoptosis of carcinoma cells successfully. The results led to the following conclusions. 1) When selecting a promoter/enhancer for expression-targeted gene delivery, it is not enough to perform a microarray on some tumor tissue and select the control element associated with the greatest amount of gene up-regulation vs. normal controls. The mechanism of expression for the particular gene should be taken into account to prevent lengthy and costly research trials. 2) When overexpression is due to activator binding, a predictive model based on endogenous gene expression levels, overall cell transfectability, and cell doubling rates can be used to predict expression-targeted gene delivery outcomes with significant accuracy.	bladder
Robot-assisted partial cystectomy of a bladder pheochromocytoma.	Pheochromocytoma of the urinary bladder is an unusual tumor that typically presents with hypertensive crises related to micturition. We report here an unusual case of bladder pheochromocytoma that was treated by robotic-assisted laparoscopic partial cystectomy. A 35-year-old male patient presented with headache and hypertension related to micturition. The patient, who had a 3.5 × 4 cm solitary bladder tumor in the bladder dome, underwent robot-assisted partial cystectomy. The whole procedure was successfully performed using the robot without conversion to open surgery. The total operative time was 120 min and the estimated blood loss was 30 ml.	bladder
Cyclooxygenase 2-dependent and independent activation of Akt through casein kinase 2α contributes to human bladder cancer cell survival.	BACKGROUND: Survival rate for patients presenting muscle invasive bladder cancer is very low, and useful therapeutic target has not been identified yet. In the present study, new COX2 downstream signals involved in urothelial carcinoma cell survival were investigated in vitro and in vivo. METHODS: COX2 gene was silenced by siRNA transfection. Orthotopic implantation animal model and transurethral instillation of siRNA with atelocollagen was constructed to examine the effects of COX2 knockdown in vivo. Cell cycle was examined by flowcytoketry. Surgical specimens derived from patients with urinary bladder cancer (all were initially diagnosed cases) were used for immunohistochemical analysis of the indicated protein expression in urothelial carcinoma cells. RESULTS: Treatment with the COX2 inhibitor or knockdown of COX2 reduced expression of casein kinase (CK) 2 α, a phophorylated Akt and urokinase type plasminogen activator (uPA), resulting in p27 induction, cell cycle arrest at G1 phase and cell growth suppression in human urothelial carcinoma cell lines expressing COX2. Silencing of CK2α exhibited the similar effects. Even in UMUC3 cells lacking the COX2 gene, COX2 inhibition also inhibited cell growth through down-regulation of the CK2α-Akt/uPA axis. The mouse orthotropic bladder cancer model demonstrated that the COX2 inhibitor, meloxicam significantly reduced CK2α, phosphorylated Akt and uPA expression, whereas induced p27 by which growth and invasiveness of bladder cancer cells were strongly inhibited. Immunohistochemically, high expression of COX2, CK2α and phosphorylated form of Akt was found in high-grade, invasive carcinomas as well as carcinoma in situ, but not in low-grade and noninvasive phenotypes. CONCLUSIONS: COX2-dependent and independent activation of CK2α-Akt/uPA signal is mainly involved in urothelial carcinoma cell survival, moreover, not only COX2 but also CK2α could be direct targets of COX2 inhibitors.	bladder
[The prognostic significance of human equilibrative nucleoside transporter1 (hENT1) expression in metastatic bladder cancer patients treated with gemcitabine-cisplatin based combination chemotherapy].	Systemic combination chemotherapy, such as the methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) regimen, has shown certain activity in advanced bladder cancer, but is associated with a significant toxicity burden, with a treatment-related mortality of about 4%. Therefore, a great deal of interest has been focused on the gemcitabine-cisplatin (GC) combination chemotherapy which showed the same antitumor effect as MVAC chemotherapy with far less toxicity. Indeed, the GC regimen is now frequently administered as the first-line chemotherapy against metastatic bladder cancer. For the present, GC/MVAC regimens constitute alternative platform chemotherapy, until new evidence based strategy can be demonstrated. Accordingly it is important to be able to predict whether a regimen is effective in each patient with bladder cancer before the initiation of chemotherapy. Clinicopathological factors as the Karnofsky performance status and the presence of visceral metastases are well-established prognostic markers for poor survival. However, they are inadequate to predict the optimal therapeutic regimen for each individual patient. As for the predictive marker of cisplatin, ERCC1 may predict survival in bladder cancer treated by platinum-based therapy. The predictive potential of gemcitabine has not been previously considered in advanced bladder cancer treated by gemcitabine-combined systemic chemotherapy. In our retrospective study, the predictive value of a high expression level of hENT1 was assessed in bladder cancer treated by gemcitabine combined combination chemotherapy.	bladder
GSTM1, GSTT1 null variants, and GPX1 single nucleotide polymorphism are not associated with bladder cancer risk in Egypt.	BACKGROUND: Bladder cancer is the most common male malignancy in Egypt, consists predominantly of urothelial cell carcinoma (UCC) and squamous cell carcinoma (SCC), and disparities in incidence exist between men and women regardless of geographic region. Tobacco smoke exposure and Schistosoma haematobium (SH) infection and the presence of GSTM1, GSTT1, and GPX1 genotypes, as modulators of the carcinogenic effect of reactive oxidative species, were hypothesized to modify bladder cancer risk and possibly explain these gender differences. METHODS: We evaluated the association between bladder cancer risk and functional polymorphisms in the GSTM1, GSTT1, and GPX1 genes in 625 cases and 626 matched population-based controls in Egypt and assessed for potential interactions between these candidate genes and environmental exposures, such as smoking and SH infection. We analyzed the risk for developing UCC and SCC separately. RESULTS: None of these functional polymorphisms were significantly associated with bladder cancer risk. There were no significant interactions between genotypes and smoking or SH infection in this population, nor was any difference detected in genotypic risk between men and women. CONCLUSIONS: Our findings suggest that common genetic variations in GSTM1, GSTT1, and GPX1 are not associated with bladder cancer risk overall and that well-known environmental risk factors, such as smoking and SH infection, do not interact with these genes to modulate the risk. IMPACT: Our data indicate that common genetic variations in GSTM1, GSTT1, and GPX1 were not associated with bladder cancer risk.	bladder
Detection of bladder cancer using novel DNA methylation biomarkers in urine sediments.	BACKGROUND: Bladder cancer (BCa) remains a lethal malignancy that can be cured if detected early. DNA hypermethylation is a common epigenetic abnormality in cancer that may serve as a marker of disease activity. METHODS: We selected 10 novel candidate genes from the most frequently hypermethylated genes detected by DNA microarray and bisulfite pyrosequencing of bladder cancers and applied them to detect bladder cancer in urine sediments. We analyzed DNA methylation in the candidate genes by quantitative methylation-specific real-time PCR (qMSP) to detect bladder cancer in urine sediments from 128 bladder cancer patients and 110 age-matched control subjects. RESULTS: Based on a multigene predictive model, we discovered 6 methylation markers (MYO3A, CA10, SOX11, NKX6-2, PENK, and DBC1) as most promising for detecting bladder cancer. A panel of 4 genes (MYO3A, CA10, NKX6-2, and DBC1 or SOX11) had 81% sensitivity and 97% specificity, whereas a panel of 5 genes (MYO3A, CA10, NKX6-2, DBC1, and SOX11 or PENK) had 85% sensitivity and 95% specificity for detection of bladder cancer (area under curve = 0.939). By analyzing the data by cancer invasiveness, detection rate was 47 of 58 (81%) in non-muscle invasive tumors (pTa, Tis, and pT1) and 62 of 70 (90%) in muscle invasive tumors (T2, T3, and T4). CONCLUSIONS: This biomarker panel analyzed by qMSP may help the early detection of bladder tumors in urine sediments with high accuracy. IMPACT: The panel of biomarker deserves validation in a large well-controlled prospectively collected sample set.	bladder
[Expression and significance of macrophage migration inhibitory factor in bladder urothelial cell carcinoma].	OBJECTIVE: To evaluate the expression and clinical significance of macrophage migration inhibitory factor (MIF) in patients with bladder urothelial cell carcinoma. METHODS: Immunohistochemical staining for MIF was performed on tissue sections of 110 patients with bladder urothelial cell carcinoma and 10 normal controls, and the correlations between MIF and clinicopathological characteristics and prognosis were also analyzed. RESULTS: Normal bladder urothelium from control subjects showed negative or weak staining of MIF. Of the cancer specimens, 72/110 (65.5%) showed a moderate to strong staining of MIF. The expression of MIF protein was found predominantly in the tumor cell cytoplasm and inversely correlated with tumor stage. 27 cases also showed a positive intranuclear staining of MIF, which was inversely correlated with tumor grade, stage and tumor size. Kaplan-Meier analysis showed that the expression of MIF in the cell nuclei was associated with disease-free survival for the cancer patients, but multivariate analysis showed that MIF was not an independent prognostic factors. CONCLUSIONS: The expression of MIF in non-muscle invasive bladder cancer tissues was more frequently than that in muscle-invasive disease, the positive staining of MIF in cell nuclei might be a favorable biomarker for patients with bladder urothelial cell carcinoma.	bladder
Primary adenocarcinoma of the urinary bladder: value of cell cycle biomarkers.	Primary adenocarcinomas of the urinary bladder are uncommon, and the molecular pathways are currently not well defined. In this study, we assessed the association between biologic markers and clinicopathologic characteristics in a cohort of 21 patients with primary urinary bladder adenocarcinoma. Immunohistochemical staining for cell cycle-specific markers, including p53, p21, p27, Ki-67, and cyclin E, were performed on sections of a tissue microarray construct. The tumors were high grade in 12 (57%) and pT2 or higher in 18 (86%); lymph nodes were involved in 6 cases (29%); and there was pathologic evidence of schistosomiasis in 14 (67%). The best prognostic combination of markers was combined alterations in p27 and Ki-67 and was associated with stage (P = .012), grade (P = .005), DNA ploidy (P = .005), and lymph node involvement (P = .04). Stage, lymph node involvement, combined alterations of p27 and Ki-67, and combined alterations of all 5 biomarkers were associated with increased probability of disease recurrence and cancer-specific mortality (P < .05).	bladder
A Surveillance, Epidemiology, and End Results analysis of small cell carcinoma of the bladder: epidemiology, prognostic variables, and treatment trends.	BACKGROUND: Small cell carcinoma of the urinary bladder (SCCB) is difficult to characterize and study because of its rarity. For the current study, a large population-based database was used to address ill-defined clinical parameters for this disease. METHODS: The authors analyzed the incidence, sociodemographics, prognostic variables, and treatment trends of this cancer in the Surveillance, Epidemiology, and End Results (SEER) limited database (1991-2005). The SEER-Medicare database (1991-2005) was used to estimate chemotherapy use. RESULTS: There were 642 patients in the SEER limited dataset. From 1991 to 2005, the incidence of SCCB increased significantly from 0.05 to 0.14 cases per 100,000 population (P < .01; approximately 500 new cases of SCCB per year, representing 0.7% of all bladder malignancies). The median overall survival was 11 months. Elderly Caucasian men were the most commonly affected (ratio of Caucasians to non-Caucasians, 10:1; ratio of men to women, 3:1; median age, 73 years). Age, race, marital status, and TNM staging were identified as independent prognostic variables (P < .05). Patients who had stage IV disease without distant metastasis (ie, positive lymph node status) had overall and cancer-specific survival rates similar to those of patients who had stage I through III disease, but they had significantly better survival compared with patients who had distant metastasis (P < .0001). Transurethral resection of the bladder tumor became the most common surgical treatment (P < .0001), representing 55% of patients from 2001 to 2005. The receipt of radiation and chemotherapy did not change significantly during the study period. CONCLUSIONS: These comprehensive data delineated the patient population for this rare disease, described several independent prognostic variables, and demonstrated clear treatment trends for this disease. The results suggest that a simpler staging system (ie, limited stage vs extensive stage) may be appropriate for patients with SCCB.	bladder
Factors affecting valrubicin response in patients with bacillus Calmette-Guérin-refractory bladder carcinoma in situ.	OBJECTIVE: Patients with bacillus Calmette-Guérin (BCG)-refractory carcinoma in situ (CIS) of the bladder are candidates for intravesical (IVe) valrubicin. This post-hoc analysis of data from the pivotal phase 3, prospective, open-label study of valrubicin evaluated the effects of patient characteristics and past treatments on the response to valrubicin. METHODS: Enrolled patients had non-muscle-invasive CIS with or without concurrent papillary disease stage Ta and/or T1 for which papillary tumors had been resected before treatment, and had previously received ≥ 2 courses of IVe therapy (≥ 1 BCG course). Patients received a course of valrubicin, which consisted of 6 weekly IVe treatments of valrubicin (800 mg). Complete response was defined as no evidence of disease by urine cytology, cystoscopy, and biopsy at 3 and 6 months posttreatment. Patient characteristics, baseline urinary symptoms, and number and type of previous treatment courses and instillations were compared for complete versus nonresponders (including partial responders) to valrubicin. RESULTS: Ninety patients enrolled; 87 patients with positive biopsy at initiation completed a valrubicin course and underwent the 3-month assessment. Five had missing data at 6 months. Of the remaining 82 patients, 18 demonstrated a complete response; 64 demonstrated partial or no response. For complete responders versus partial or nonresponders, differences in patient characteristics, baseline urinary symptoms, and number of previous courses or instillations of BCG or other types of treatment were not significant (P > 0.05). More complete responders had evidence of inflammation before or during valrubicin treatment (P = 0.005 vs nonresponders). CONCLUSIONS: In these patients with BCG-refractory CIS, complete responders to valrubicin did not differ significantly from partial or nonresponders in the number of prior courses or instillations. The results suggest that therapy with valrubicin may be considered in appropriate candidates who have not responded to prior therapies. Cystectomy should be reconsidered when valrubicin treatment fails.	bladder
Frailty modelling for survival data from multi-centre clinical trials.	Despite the use of standardized protocols in, multi-centre, randomized clinical trials, outcome may vary between centres. Such heterogeneity may alter the interpretation and reporting of the treatment effect. Below, we propose a general frailty modelling approach for investigating, inter alia, putative treatment-by-centre interactions in time-to-event data in multi-centre clinical trials. A correlated random effects model is used to model the baseline risk and the treatment effect across centres. It may be based on shared, individual or correlated random effects. For inference we develop the hierarchical-likelihood (or h-likelihood) approach which facilitates computation of prediction intervals for the random effects with proper precision. We illustrate our methods using disease-free time-to-event data on bladder cancer patients participating in an European Organization for Research and Treatment of Cancer trial, and a simulation study. We also demonstrate model selection using h-likelihood criteria.	bladder
FDG PET/CT incidental diagnosis of a synchronous bladder cancer as a fourth malignancy in a patient with head and neck cancer.	A 74-year-old man with 40-year history of smoking and known history of chronic lymphocytic leukemia and cutaneous T-cell lymphoma underwent FDG PET/CT examination for a recent diagnosis of squamous cell carcinoma diagnosed from right frontal crown and left posterior ear skin biopsy. PET images revealed multiple FDG-avid lesions in the head and neck, highly suspicious for nodal metastases. Reviewing CT portion of PET/CT examination revealed a hyperattenuating density in the posterior bladder wall. This lesion was not noticed initially due to the intense physiologic bladder uptake. On lowering the intensity, this lesion showed intense FDG avidity on the PET portion of the examination. Cytoscopic biopsy revealed low-grade papillary urothelial cell carcinoma.	bladder
Phase II study of biweekly gemcitabine as first line therapy in CIS of the bladder: what does an aborted trial tell us?	OBJECTIVE: The objective of this study was to challenge the activity of a promising intravesical drug (gemcitabine), administered at an intensive regimen (2,000 mg twice a week for 6 weeks) in treatment naïve CIS of the bladder and to observe side-effects. The statistical design was conceived to provide sufficient information through the enrollment of a low number of patients. MATERIAL AND METHODS: Primary, secondary, and concurrent CIS with no prior intravesical therapy were eligible. Treatment schedule: 2000 mg gemcitabine in 50 ml saline, unbuffered, for 1 hour twice a week for 6 weeks. Complete response (CR) = negative cytology and negative cystoscopy + bladder mapping at 3 months. Failure (FA) = all other situations. Side-effects were recorded according to Common Terminology Criteria for Adverse Events (CTCAE). STUDY DESIGN: A 3-stage design. After testing the drug on 11 patients in the first stage, the trial had to be terminated if 3 or fewer CRs. After testing the drug on 21 patients in the first and second stages, the trial had to be terminated if 7 or fewer CRs. After testing the drug on 32 patients in all 3 stages, the drug was considered active in case of >12 CRs. Survival data up to 4 years from trial closure were collected. RESULTS: The study proceeded to stage II since 5/11 responded at stage I but it was stopped after including 18 patients due to side-effects; 6/18 had primary CIS, 7 had secondary CIS, and 5 concomitant CIS; 6/18 (33.3%) had grade 3 side-effects (4 G3 cystitis, 3 G3 leucopenia), leading to stopping the treatment in all 6 cases. CRs were observed in 8/18 patients (44.4%), FA in 10/18 (55.5%). Median overall survival (OS) was 44 months with a 4-year cancer-specific survival of 100%. CONCLUSION: Biweekly gemcitabine as first line treatment for CIS led to excess toxicity and suboptimal activity. Due to the peculiar statistical design, a negative response was generated enrolling a low number of patients. The absolute 4-year CSS suggests that no window of opportunity for disease cure may have been lost by assessing a new, non standard, treatment for CIS.	bladder